2-20202619-C-T

Variant names:

• chr2-20202619-C-T
• rs1131351
• NM_002997.5:c.*147G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002997.5(SDC1):​c.*147G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000691 in 622,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000069 (0 hom.)
• Consequence: SDC1 NM_002997.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400
• Publications: 16 publications found

Genes affected

SDC1 (HGNC:10658): (syndecan 1) The protein encoded by this gene is a transmembrane (type I) heparan sulfate proteoglycan and is a member of the syndecan proteoglycan family. The syndecans mediate cell binding, cell signaling, and cytoskeletal organization and syndecan receptors are required for internalization of the HIV-1 tat protein. The syndecan-1 protein functions as an integral membrane protein and participates in cell proliferation, cell migration and cell-matrix interactions via its receptor for extracellular matrix proteins. Altered syndecan-1 expression has been detected in several different tumor types. While several transcript variants may exist for this gene, the full-length natures of only two have been described to date. These two represent the major variants of this gene and encode the same protein. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BS2: High AC in GnomAdExome4 at 43 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDC1	NM_002997.5	c.*147G>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000254351.9	NP_002988.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDC1	ENST00000254351.9	c.*147G>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_002997.5	ENSP00000254351.4
SDC1	ENST00000403076.5	c.479-318G>A		intron_variant	Intron 3 of 3	1		ENSP00000384613.1
SDC1	ENST00000381150.5	c.*147G>A		3_prime_UTR_variant	Exon 6 of 6	5		ENSP00000370542.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000691 AC: 43 AN: 622596 Hom.: 0 Cov.: 8 AF XY: 0.0000768 AC XY: 25 AN XY: 325574

African (AFR) AF: 0.00 AC: 0 AN: 16130

American (AMR) AF: 0.00 AC: 0 AN: 26506

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15148

East Asian (EAS) AF: 0.000486 AC: 17 AN: 34998

South Asian (SAS) AF: 0.000328 AC: 17 AN: 51908

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2408

European-Non Finnish (NFE) AF: 0.0000148 AC: 6 AN: 404242

Other (OTH) AF: 0.0000941 AC: 3 AN: 31866

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 898

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	9.1
DANN	Benign	0.96
PhyloP100		-0.040
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1131351; hg19: chr2-20402380;